We propose to continue our studies of the cell physiology of secretion and of the pathogenesis and exocrine gland dysfunction of cystic fibrosis. The cellular physiological, pharmacological and biochemical aspects of secretion will be studied in vitro, using enzymatically dispersed but morphologically and functionally intact acinar cells from the parotids of the rat and man. Specifically, the proposed studies will include: (1) Continuation of the investigation of ion transport and autonomic receptor physiology and pharmacology of rat parotid acinar cells; (2) Preservation of these cells on floating collagen membranes under conditions of cell culture; (3) Induction of proliferation of these cells; (4) Study of cell physiology and pharmacology of human parotid acinar cells using the methods applicable to the rat parotid acinar cells; (5) Study of the cell physiology of parotid acinar cells obtained from patients with cystic fibrosis after death; (6) Attempts to induce in control human and rat parotid acinar cells changes similar to those seen in cystic fibrosis; and (7) In vivo induction of pharmacological models of cystic fibrosis (chronic use of isoproterenol or reserpine) and subsequent study of the isolated parotid acinar cells in vitro.